I'm not clear what you are asking. Even 2500 x 2500 is already insane. Unless you are working on ultra high res panoramas or something like that I can't picture a single scenario where anyone would need such crazy large brushes. The rest can't be answered without seeing your image. There may be a million different ways to isolate and recolor the areas you want to paint over and fill them or tweak them with adjustments.
Mylenium