You can easily update the code and map elements of your game with a simple reboot. Modifying any sound or art assets while the game is running or introducing new ones to the code or map will cause the .rsc to lock up. You WILL have to close the server if you modify the resources.
From what I understand preload_rsc allows you to specify different locations you can download resources from. They still have to be present within the game itself though, so I don't think it would work. I've never experimented with it so I may be wrong.
I've modified the .rsc file with the game running. I don't know if it's safe, but you can drag the .dmb and .rsc into the folder containing the host files and it won't complain about the .rsc being locked. This method requires that you're not hosting from the source, of course, otherwise you can't compile.