Here's a few ideas:
Have your Layout Main events grouped
in Layout Start > Start of Layout > Set Layout Main group inactive
in Layout Main > Start of Layout > Set Layout Main group active
Have a global variable "Game_Started" set to 1 once you go to Layout Main; only start your spawns or main game events if Game_Started = 1
If you are using Time Delta (which you should be if possible):
in Layout Start > Start of Layout > Set time scale 0
in Layout Main > Start of Layout > Set time scale 1
I think setting groups of events to active / inactive is the easiest solution (groups can also be nested). Hope that helps.