It depends on what you mean by substantial. Considering your question spans some 300 years and territories spread through three continents, there certainly were spaniards migrating to and settling in Portuguese America during the colonial era (and vice versa), but the numbers vary according to the "where" and "when".
Despite this, it's safe to say there generally were near to no areas under Lusitan control that had a large relative number of Spanish people when compared to Portuguese settlers, local natives or african slaves. This was thanks to a lot of factors mostly having to do with rivalries between the iberian kingdoms, developing national identities and the particularities of hispano-portuguese social, economical, legal and political structures at the time. All of these stimulated Portugal's subjects to remain on areas controlled by the Portuguese crown, and the same was true for the Spanish. This means that most of the spaniards who came to Brazil did so individually or as part of small groups, and were mostly those who would have had an incentive to take part on the Atlantic travels in some capacity, but for one reason or another didn't develop strong ties to Spanish institutions and territorries.
There are two notable situations that are exceptions to this general tendency, though. The first one was during the Iberian Union (1580-1640), when Portugal and Spain were made into a composite monarchy under Habsburg rule. Even if both kingdoms got to preserve their institutions, laws and governmental structures, while the union lasted there were to be no official policies to discourage Spanish subjects from settling in Brazil, and a contingent of (mostly) Castillians did so. While this was noted to be an expressive increase in Spanish migration to captaincies such as São Vicente, there is no consensus on even the possibility to measure numbers with any accuracy - especially since most of those new arrivals integrated fully into local society, marrying native women, adopting local Portuguese names, customs and language, so their presence became mostly unnoticeable in the long term.
The second exception was the territory around what is today the Triple Frontier between Brazil, Argentina and Paraguay. The region was under dispute up to the latter half of the 1800's. Borders were blurred and difficult to enforce in an area with almost no natural barriers, so control of the land changed hands often between Portuguese and Spanish governments. They also had to account for and try to negotiate alliances with the native indigenous peoples if they intended to safeguard their conquests. Not only that, but there was heavy jesuit presence in the area, represented by the reductions, settlements where they took in the indigenous people for religious conversion efforts, and from where they eventually rebelled in 1756. In such an ambiguous territory, there was a good mix of Portuguese, Spanish and natives among the population in any given area, be them under the control of the Lusitan or Castillian crowns.
Bibliography:
"A "conquista" dos Sete Povos das Missões: de "ato heróico" dos luso-brasileiros a campanha negociada com os índios.", by Elisa Frühauf Garcia.
"História da Vida Privada no Brasil, vol. 1", By Fernando A. Novais and Laura de Mello e Souza (orgs).
Edited to add the volume on the bibliography.