Alexander was not the first to attack the Persian Empire from the West, and each previous attempt (during the Ionian Revolt in 499-494 BC, by the Athenians in 479-448 BC, and by the Spartans in 399-394 BC) was handled by the Great King's subordinate commanders in the area. Even if they failed to contain the threat, they were simply replaced with new representatives of the throne. Apparently the Persian King would not concern himself with so remote a region unless things got seriously out of hand.