Hi
@DevinFC,
Currently, this is not possible. The baking takes place when the game content is cooked through the editor. We are currently looking into ways to optimize the plugin both with performance and memory usage.
Being able to drop the Substance functionality when no longer used would be a great feature and something we will look into adding support for.
As for the memory usage you are seeing, just to get a better understanding, how many Substances were used in this test scene? Are you using the GPU or CPU Substance Engine?
"If you bake the material, shouldn't the result be just as expensive as old-fashioned textures?" You are very correct but the default Texture2D objects stream texture data. This is something we are also working to bring support for.
I am sorry that we do not have a solution today but we will in the near future. I can post an update here when this is the case.

Cheers!